Bone Abstracts

RANKL induced osteoclastogenesis is mediated by several transcription factors such as NF-κB, AP-1 and Nfatc1. We have found that also cysteine proteinases are involved in the signaling pathway downstream RANK. Thus, cystatin C, Z-RLVG-CHN2 (the sequence of which is based upon one of the enzyme inhibitory domains in cystatin C) and the fungal molecule E-64 – inhibit RANKL induced mouse and human osteoclast formation in vitro (Strålberg et ...

Objective: Increase the percentage of elderly fracture patients undergoing a dual energy X-ray absorptiometry (DXA) measurement, and investigate why some patients did not respond to invitation to our fracture liaison service (FLS).Materials and methods: In four Dutch hospitals, fracture patients ≥50 years were invited for a DXA measurement and visit to our FLS. Patients who did not respond, were contacted by telephone. In patients diagnosed with os...

Background and methods: A specific skeletal complication in children with CKD is growth impairment. The effects of recombinant human growth hormone (rhGH) therapy on bone turnover and bone material quality are not well understood. Bone matrix mineralization density distribution (BMDD) as assessed by quantitative backscattered electron microscopy (qBEI) is an important determinant of bone material quality and reflects bone turnover (average tissue age) and mineralization kineti...

Recent studies have demonstrated that the global or osteoblast-specific deletion of neuropeptide Y Y1 receptor (Y1R), as well as the pharmacological blockade of Y1R, leads to pronounced anabolic effects in bone metabolism. This suggests that anti-Y1R drug therapy might have clinical applications for the prevention/recovery of bone loss occurring in osteoporosis. Given the high fracture incidence in this target population, it remained...

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Classical osteogenesis imperfecta (OI) is caused by mutations in the two genes encoding type I collagen. OI is associated with low bone mass and abnormally high bone matrix mineralization. The Brtl/+ OI mouse is a knock-in model caused by a glycine substitution in one COL1A1 allele. Brtl/+ pups display 30% perinatal lethality; survivors have small size and brittle bone. Unexpectedly, homozygous Brtl/Brtl pups, producing only mutant collagen, have normal survival rates...

Introduction: Elevated FGF-23 serum levels are induced by hyperphosphatemia and are linked to poor skeletal mineralization and adverse outcomes including vascular calcification and mortality. Recently, it was shown that FGF-23 levels are substantially elevated in acute kidney injury (AKI), and that higher levels in AKI are associated with a greater risk of adverse outcomes.Methods: In 25 vitamin D deficient (25(OH)D <20 ng/ml) critically ill adults w...

In clinical studies, denosumab (DMAb) administration up to 8 years is associated with continued increases in bone mineral density (BMD) and low fracture incidence despite persistently low bone turnover markers and limited iliac crest tetracycline labelling (Papapoulos 2013). We tested the hypothesis that, with persistently low bone remodelling, BMD increases may result from a non-remodelling dependent mechanism to accrue bone matrix. We examined the fluorochrome labelling patt...

Mutations in LRP5 cause a variety of phenotypes, including high bone mass and low bone mass disorders. In patients with high bone mass, different heterozygous mutations have been described, all of them clustering in a region including the binding pocket for DKK1 and sclerostin. The pathogenic mechanism is thought to be a gain-of-function mediated by an impaired inhibition of the canonical Wnt signalling pathway, thereby leading to increased bone modelling.<p class="abstext...

Transient receptor potential vanilloid channels (TRPVs) have been implicated in Ca2+ homeostasis and bone metabolism. In particular, TRPV4 deficiency was shown to cause sexual dimorphism in bone metabolism and osteoporotic fracture risk. Cortical bone structure was reported to be altered in male TRPV4 knock-out (TRPV4−/−) mice but not in female TRPV−/− mice compared to sex-matched wildtype (TRPV4+/+) animals.To gain knowledge on t...